The major aim is to broaden our understanding of how the adult pattern of precise and orderly connections in the mammalian CNS is achieved during development. Order in the adult CNS is exemplified in the mammalian visual system, and the research is centered around the question, "How is the orderly pattern of connections between retina, lateral geniculate nucleus (LGN), and primary visual cortex established during the fetal and postnatal development of the cat's visual system?" Four specific areas are under study. 1.) The cellular interactions that occur between the axons of retinal ganglion cells and their target LGN neurons during the prenatal development of the eye-specific layers within the LGN are being studied by means of electron microscopy combined with the in vitro labeling of individual retinogeniculate axons. 2.) The development of the geniculocortical projection is being studied, with particular emphasis on the early period during which LGN axons wait in a special transient embryonic zone called the subplate, located just below the developing cortical plate. The morphological changes, functional and topographic development of geniculocortical axons are being studied by means of in vitro anatomy and physiology, electron microscopy, and retrograde tracing techniques. 3.) The role of the subplate in the development of the cerebral cortex is being studied. The identities of the cellular constituents of the subplate and their prenatal development and postnatal disappearance are being studied by means of 3H-thymidine autoradiography, electron microscopy, in vitro physiology, retrograde tracing, and a variety of useful immunohistochemical markers including antibodies against neuropeptides and synaptic vesicle antigens. Experiments designed to delete subplate cells in order to examine the effect on cortical development are also proposed. 4.) The abnormal development of connections between LGN and cortex in Siamese cats is being studied by means of transneuronal autoradiography and retrograde transport. In these animals, connections between retina, LGN and cortex have been systematically altered due to a genetic mutation, thereby providing the opportunity to compare normal with abnormal development. Results from the studies are expected to add not only to knowledge of visual system development, but also to our general understanding of how specific connections are formed in the nervous system, including the human nervous system.